Colthorpe P, Farr S J, Smith I J, Wyatt D, Taylor G
Welsh School of Pharmacy, University of Wales College of Cardiff, United Kingdom.
Pharm Res. 1995 Mar;12(3):356-9. doi: 10.1023/a:1016292232513.
The pulmonary deposition and pharmacokinetics of human growth hormone (hGH), administered by aerosol and instillate, in formulations containing 99mTc-DTPA (for gamma scintigraphic imaging) have been studied in five male New Zealand White rabbits. Gamma scintigraphy indicated that the peripheral:central deposition tended to be greater for aerosol (1.54) than for instillate (0.8). Two gamma scintigraphic methods were used to quantify dose deposited by aerosol, which permitted bioavailabilities to be determined. The bioavailable fraction for aerosolized hGH (45%) was greater than for instilled hGH (16%). This was attributed to the differential effects of mucociliary clearance. Absorption rate limited pharmacokinetics prevailed for both hGH formulations with post-peak half-lives approximately 10-fold greater than the intravenous elimination half-life of 40 min. Apparent absorption rate constants resulting from instillation and aerosolization were equivalent (0.0012 min-1 and 0.0020 min-1 respectively), however lung-to-blood transfer rate constants for aerosol delivery (0.00071 min-1) were greater than for instillation (0.00018 min-1).
在五只雄性新西兰白兔中，研究了通过气雾剂和滴注方式给予含99mTc-DTPA（用于γ闪烁显像）制剂的人生长激素（hGH）的肺部沉积和药代动力学。γ闪烁显像表明，气雾剂的外周：中央沉积倾向（1.54）大于滴注（0.8）。使用两种γ闪烁显像方法对气雾剂沉积的剂量进行定量，从而能够确定生物利用度。雾化hGH的生物可利用部分（45%）大于滴注hGH（16%）。这归因于黏液纤毛清除的不同作用。两种hGH制剂均呈现吸收速率限制的药代动力学，峰后半衰期比静脉消除半衰期40分钟大约长10倍。滴注和气雾化产生的表观吸收速率常数相当（分别为0.0012分钟-1和0.0020分钟-1），然而气雾剂给药的肺到血转运速率常数（0.00071分钟-1）大于滴注（0.00018分钟-1）。
